Radioimmunotherapy of patients with cutaneous T-cell lymphoma using an iodine-131-labeled monoclonal antibody: analysis of retreatment following plasmapheresis

Radioimmunotherapy retreatment of patients receiving radiolabeled murine monoclonal antibodies is difficult because of human antimurine antibody (HAMA) formation. Retreatment therapy was initiated in three patients at the time of disease progression using a radioiodinated monoclonal antibody (T101). The clinical protocol consisted of a two day plasma exchange (4-6 L) to reduce HAMA titers. Immunoimaging was performed with 5 mCi 131I-T101 (10 mg). Gamma scintillation images were obtained 18 hr postinfusion, and radiation dosimetry estimates were performed. At 24 hr postinfusion, each patient received a 100-mCi 131I-T101 (10 mg) therapy dose. Results obtained after plasmapheresis showed a significant reduction, ranging from 28%-61%, in HAMA titers. Blood clearances were markedly different between initial therapy and retreatment therapy for patient with high HAMA titers, reflecting immune complex formation. Two patients responded to retreatment therapy with responses lasting 1 to 2 mo. Minimal acute and no chronic toxicities were observed during the retreatment protocol.     

Role of viruses in the induction of primary intracranial tumors

The role of viruses in the induction of primary intracranial tumors is reviewed. Papovaviruses of the simian virus 40 (SV40) group are used as a representative model, and a distillation of the literature on virus induction of intracranial tumors in laboratory animals and neoplastic transformation of cells in culture is presented. The molecular sequence of events during tumor induction and neoplastic cell transformation is also discussed. Recent evidence that the papovaviruses play a role in the formation of human brain tumors is summarized.     

Modelling the differences in counted outcomes using bivariate copula models with application to mismeasured counts*

Summary This paper makes three contributions. Firstly, it uses copula functions to obtain a flexible bivariate parametric model for non‐negative integer‐valued data (counts). Secondly, it recovers the distribution of the difference in the two counts from a specified bivariate count distribution. Thirdly, the methods are applied to counts that are measured with error. Specifically, we model the determinants of the difference between the self‐reported number of doctor visits (measured with error) and true number of doctor visits (also available in the data used).     

Treatment of donor T cell-mediated hematopoietic suppression after haploidentical bone marrow transplantation by T cell modulation in a patient with severe combined immunodeficiency.

An 8-month-old male patient with severe combined immunodeficiency syndrome was transplanted with maternal, haploidentical T cell-depleted bone marrow without prior conditioning therapy. Acute graft-versus-host disease developed 2 weeks post bone marrow transplantation (BMT) and was successfully treated with cortisone. After cortisone withdrawal the patient developed myeloid and B cell depression concomitant with T cell activation. For specific T cell modulation, treatment with the T cell receptor (TCR) alpha beta chain-binding MoAb BMA031 was initiated in combination with cyclosporin A. GM-CSF was given to enhance myeloid reconstitution. About 1 year post BMT, B cell and granulocyte counts were within the normal range with stable chimerism in both lineages. B cell proliferation tests were normal and first signs of in vitro immunoglobulin synthesis occurred.     

Neuroactive amino acids in organotypic slice cultures of the rat hippocampus: an immunocytochemical study of the distribution of GABA, glutamate, glutamine and taurine.

Antisera raised against protein-glutaraldehyde-amino acid conjugates were used to study the light and electron microscopic distribution of GABA, glutamate, glutamine and taurine in organotypic slice cultures of rat hippocampi. In the stratum oriens and radiatum, glutamate-like immunoreactivity was particularly concentrated in nerve endings establishing asymmetric junctions with dendritic spines. Mossy fiber terminals in CA3 and the dentate hilus were also strongly labeled. A quantitative immunogold analysis of the glutamate-immunolabelled profiles showed a pattern that was highly reminiscent of that previously observed in perfusion-fixed hippocampi, including a correspondingly sparse labeling of glial processes and of presynaptic elements in symmetric synapses. GABA-like immunoreactivity was localized predominantly in interneurons and in presynaptic terminals contacting dendritic shafts and neuronal cell bodies, while immunoreactivities for glutamine and taurine were found mainly in astroglial cells and pyramidal cells, respectively. Our data indicate that the major intrinsic fiber systems of the cultured hippocampi have retained their normal transmitter phenotypes.     

Pathways to Disability Income among Persons with Severe, Persistent Psychiatric Disorders

Persons with psychiatric disorders comprise the largest diagnostic group of disabled recipients of Supplemental Security Income (SSI) and Social Security Disability Income (SSDI). A 32-month prospective cohort study of pathways to application for and receipt of SSI and SSDI was conducted among 169 people with major psychiatric disorders who were at an early stage of their illness and who had never applied for or received disability income. Of the three pathways that formed the conceptual basis for the investigation—labeling, impairment, and needs/resources—the latter two emerged as significantly associated with receipt. Individuals with more severe symptoms who were African American, and who were psychologically dependent in a primary relationship and financially dependent on their families, were more likely to become recipients. Enabling and disabling aspects of disability income receipt suggest that it may be replacing prolonged hospitalization as the most enduring social role of persons with severe, persistent psychiatric disorders.     

Amniotic sac,fetal heart area,fetal curvature,and other morphometrics using first trimester vaginal ultrasonography and color Doppler imaging.

Ultrasonographic morphometric measurements were obtained with transvaginal ultrasonography from 121 patients with first trimester singleton pregnancies. Amniotic and gestational sac diameters, fetal heart area, and fetal length increased in a linear rate relative to crown-rump length, whereas the amniotic and gestational sac volumes increased at an exponential rate. The yolk sac exhibited a biphasic growth pattern with a peak at a crown-rump length of 3.5 cm. The ratio of crown-rump length to anteroposterior dimension increased over the first trimester, suggesting less curvature in older fetuses. In conclusion, vaginal ultrasonography permits accurate measurement of many new morphometric parameters.     

Postcesarean Section Pain Prediction by Preoperative Experimental Pain Assessment

Background: Postcesarean section pain is a common cause of acute pain in obstetrics, yet pain relief and patient satisfaction are still inadequate in many cases. The present study was conducted to determine whether preoperative assessment of experimental pain perception by quantitative sensory tests could predict the level of postcesarean section pain.

Methods: Fifty-eight women who were scheduled for elective cesarean section were enrolled in the study. Heat pain threshold and magnitude estimation of suprathreshold pain stimuli at 44[degrees]-48[degrees]C were assessed for both algosity (the sensory dimension of pain intensity) and unpleasantness 1 or 2 days before surgery. The day after the operation, the women reported the level of pain at the surgical wound on a visual analog scale at rest and during activity. Regression analysis was performed to evaluate the usefulness of preoperative scores in predicting postcesarean section pain.

Results: Postoperative visual analog scale scores at rest and during activity significantly correlated with preoperative suprathreshold pain scores at 44[degrees]-48[degrees]C (r = 0.31-0.58 for algosity and r = 0.33-0.74 for unpleasantness). The stimulus of 48[degrees]C was found to be the best predictor of postoperative pain for both conditions (r = 0.434-0.527;P < 0.01). In contrast to suprathreshold pain stimuli, pain threshold was not correlated with postoperative pain.     

Catecholamine-induced cardiac hypertrophy: significance of proto-oncogene expression

The effect of β- and α-adrenergic stimulation on cardiovascular function and development of cardiac hypertrophy was studied in rats by measuring the heart weight/body weight and cardiac RNA/DNA ratios. β-Receptor stimulation with isoproterenol over 3 days induced an increase in the biosynthesis of cardiac adenine nucleotides, myocardial protein synthesis, and the heart weight/body weight ratio. The isoproterenol-induced metabolic effects were prevented by simultaneous β-adrenergic blockade with propranolol. α-Adrenergic stimulation with norfenephrine for 3 days induced an increase in heart rate, total peripheral resistance, the myocardial RNA/DNA, and left ventricular weight/body weight ratio. The calcium antagonist verapamil prevented the hemodynamic changes but did not influence the development of cardiac hypertrophy. The α-adrenergic blocker prazosin reversed the norfenephrine-induced functional changes and prevented cardiac hypertrophy. Norepinephrine was infused into isolated perfused working rat hearts to elucidate some molecular biological changes that precede the development of cardiac hypertrophy. It increased transiently and sequentially the mRNA of c-fos and c-myc. This enhancement occurred at about the same time as that induced by elevation of pre- and afterload but was more pronounced. These findings were compared with those obtained in other studies assessing the effects of catecholamines on proto-oncogene expression. Combination of norepinephrine with pre- and afterload elevation induced the c-fos mRNA signal to appear earlier, to be more pronounced, and to persist for a longer period of time. Similar results were obtained in regard to the c-myc mRNA. These findings indicate that the combination of two hypertrophy-inducing stimuli which may cause a higher degree of cardiac hypertrophy in vivo induce an earlier, more pronounced, and longer lasting expression of the proto-oncogenes c-fos and c-myc.